Change in the Usage of Complementary and Alternative Medicine in the Era of Biologics Among Korean Patients With Psoriasis.

BACKGROUND: Patients with long-standing psoriasis who are not treated with conventional medicine seek complementary and alternative medicine (CAM). The biological revolution in the field of psoriasis since the late 2000s has progressed, expecting clearance or almost clearance of the disease. The frequency and type of CAM usage may have changed after these advances. We aimed to investigate changes in CAM use in Korean patients with psoriasis before and after the prevalent use of biologics. METHODS: Patients with psoriasis who visited Pusan National University Hospitals (Busan and Yangsan) between March 2020 and June 2022 were made to complete a face-to-face structured questionnaire. These results were compared with our previous study conducted approximately 10 years ago. RESULTS: In total, 207 patients were included. Compared with the previous results, the frequency of CAM use (67.6%) increased (P < 0.001). Oriental medicine (67.1%) has most commonly been used, followed by health supplements and bath therapy. The biggest reason for using CAM was "to try all the potential treatments." Meanwhile, negative concerns about conventional medicine (13.5%) significantly decreased during the 10-year period (P < 0.001). CONCLUSION: Although treatment efficacy has increased with biologics development, CAM usage remains prevalent among Korean patients with psoriasis. Therefore, dermatologists need more efforts to improve patients' understanding of conventional medicine, including biologics.

Sensors in heart-on-a-chip: A review on recent progress.

Drug-induced cardiotoxicity is a major problem in drug discovery. Many approaches to efficient drug screening have been developed, including animal testing in vivo and cell testing in vitro. However, due to intrinsic difference between species, animal-based toxicity testing cannot comprehensively determine the potential side effects in subsequent human clinical trials. Furthermore, conventional in vitro assays are costly and labour-intensive, and require numerous tests. Therefore, it would be necessary to develop heart-on-a-chips made with advanced materials and soft bioelectronic fabrication techniques that offer fast, efficient, and accurate sensing of cardiac cells' behaviors in vitro. In this review, we introduce two key sensing methods in heart-on-a-chip for physical and electrical measurements. First, optical (e.g., direct and calcium imaging, and fluorescent, laser-based, and colorimetric sensing) and electrical (e.g., impedance, strain, and crack sensing) sensors that record the contractility of cardiomyocytes are reviewed. Subsequently, various sensors composed of rigid planar/three-dimensional electrodes, soft/flexible electronics, and nanomaterial-based transistors to monitor extracellular and intracellular electrophysiological potentials are discussed. A brief overview of future technology and comments on the current challenges conclude the review.

Heat-Generating Iron Oxide Multigranule Nanoclusters for Enhancing Hyperthermic Efficacy in Tumor Treatment.

The development of heat-generating magnetic nanostructures is critical for the effective management of tumors using magnetic hyperthermia. Herein, we demonstrate that polyethylene glycol (PEG)-coated iron oxide (magnetite, Fe3O4) multigranule nanoclusters (PEG-MGNCs) can enhance the efficiency of hyperthermia-based tumor suppression in vitro and in vivo. MGNCs consisting of granules (crystallites) measuring 22.9 nm in diameter were prepared via the hydrothermal polyol method, followed by the surface modification of MGNCs with PEG-dopamine. The freshly prepared PEG-MGNCs exhibit 145.9 ± 10.2 nm diameter on average under aqueous conditions. The three-dimensional structures of PEG-MGNCs enhance the hyperthermic efficacy compared with PEGylated single iron-oxide nanoparticles (NPs), resulting in severe heat damage to tumor cells in vitro. In the SCC7 tumor-bearing mice, near-infrared fluorescence dye (Cy5.5)-labeled PEG-MGNCs are successfully accumulated in the tumor tissues because of NP-derived enhanced permeation and retention effect. Finally, the tumor growth is significantly suppressed in PEG-MGNC-treated mice after two-times heat generation by using a longitudinal solenoid, which can generate an alternating magnetic field under high-frequency (19.5 kA/m, 389 kHz) induction. This study shows for the first time that the PEG-MGNCs greatly enhance the hyperthermic efficacy of tumor treatment both in vitro and in vivo.

CXCR2 Ligands and mTOR Activation Enhance Reprogramming of Human Somatic Cells to Pluripotent Stem Cells.

Induced pluripotent stem cell (iPSC) technology has great promise in regenerative medicine and disease modeling. In this study, we show that human placenta-derived cell conditioned medium stimulates chemokine (C-X-C motif) receptor 2 (CXCR2) in human somatic cells ectopically expressing the pluripotency-associated transcription factors Oct4, Sox2, Klf4, and cMyc (OSKM), leading to mechanistic target of rapamycin (mTOR) activation. This causes an increase in endogenous cMYC levels and a decrease in autophagy, thereby enhancing the reprogramming efficiency of human somatic cells into iPSCs. These findings were reproduced when human somatic cells after OSKM transduction were cultured in a widely used reprogramming medium (mTeSR) supplemented with CXCR2 ligands interleukin-8 and growth-related oncogene α or an mTOR activator (MHY1485). To our knowledge, this is the first report demonstrating that mTOR activation in human somatic cells with ectopic OSKM expression significantly enhances the production of iPSCs. Our results support the development of convenient protocols for iPSC generation and further our understanding of somatic cell reprogramming.

Simple and facile preparation of recombinant human bone morphogenetic protein-2 immobilized titanium implant via initiated chemical vapor deposition technique to promote osteogenesis for bone tissue engineering application.

Over the past few decades, titanium (Ti) implants have been widely used to repair fractured bones. To promote osteogenesis, immobilization of osteoinductive agents, such as recombinant human bone morphogenic protein-2 (rhBMP2), onto the Ti surface is required. In this study, we prepared rhBMP2 immobilized on glycidyl methacrylate (GMA) deposited Ti surface through initiated chemical vapor deposition (iCVD) technique. After preparation, the bio-functionalized Ti surface was characterized by physicochemical analysis. For in vitro analysis, the developed Ti was evaluated by cell proliferation, alkaline phosphatase activity, calcium deposition, and real-time polymerase chain reaction to verify their osteogenic activity against human adipose-derived stem cells (hASCs). The GMA deposited Ti surface was found to effectively immobilize a large dose of rhBMP2 as compared to untreated Ti. Additionally, rhBMP2 immobilized on Ti showed significantly enhanced osteogenic differentiation and increased calcium deposition with nontoxic cell viability. These results clearly confirm that our strategy may provide a simple, solvent-free strategy to prepare an osteoinductive Ti surface for bone tissue engineering applications.

Synergistic Oxygen Generation and Reactive Oxygen Species Scavenging by Manganese Ferrite/Ceria Co-decorated Nanoparticles for Rheumatoid Arthritis Treatment.

Poor O2 supply to the infiltrated immune cells in the joint synovium of rheumatoid arthritis (RA) up-regulates hypoxia-inducible factor (HIF-1α) expression and induces reactive oxygen species (ROS) generation, both of which exacerbate synovial inflammation. Synovial inflammation in RA can be resolved by eliminating pro-inflammatory M1 macrophages and inducing anti-inflammatory M2 macrophages. Because hypoxia and ROS in the RA synovium play a crucial role in the induction of M1 macrophages and reduction of M2 macrophages, herein, we develop manganese ferrite and ceria nanoparticle-anchored mesoporous silica nanoparticles (MFC-MSNs) that can synergistically scavenge ROS and produce O2 for reducing M1 macrophage levels and inducing M2 macrophages for RA treatment. MFC-MSNs exhibit a synergistic effect on O2 generation and ROS scavenging that is attributed to the complementary reaction of ceria nanoparticles (NPs) that can scavenge intermediate hydroxyl radicals generated by manganese ferrite NPs in the process of O2 generation during the Fenton reaction, leading to the efficient polarization of M1 to M2 macrophages both in vitro and in vivo. Intra-articular administration of MFC-MSNs to rat RA models alleviated hypoxia, inflammation, and pathological features in the joint. Furthermore, MSNs were used as a drug-delivery vehicle, releasing the anti-rheumatic drug methotrexate in a sustained manner to augment the therapeutic effect of MFC-MSNs. This study highlights the therapeutic potential of MFC-MSNs that simultaneously generate O2 and scavenge ROS, subsequently driving inflammatory macrophages to the anti-inflammatory subtype for RA treatment.

A Disposable Photovoltaic Patch Controlling Cellular Microenvironment for Wound Healing.

Electrical stimulation (ES) is known to affect the wound healing process by modulating skin cell behaviors. However, the conventional clinical devices that can generate ES for promoting wound healing require patient hospitalization due to large-scale of the extracorporeal devices. Herein, we introduce a disposable photovoltaic patch that can be applied to skin wound sites to control cellular microenvironment for promoting wound healing by generating ES. In vitro experiment results show that exogenous ES could enhance cell migration, proliferation, expression of extracellular matrix proteins, and myoblast differentiation of fibroblasts which are critical for wound healing. Our disposable photovoltaic patches were attached to the back of skin wound induced mice. Our patch successfully provided ES, generated by photovoltaic energy harvested from the organic solar cell under visible light illumination. In vivo experiment results show that the patch promoted cutaneous wound healing via enhanced host-inductive cell proliferation, cytokine secretion, and protein synthesis which is critical for wound healing process. Unlike the current treatments for wound healing that engage passive healing processes and often are unsuccessful, our wearable photovoltaic patch can stimulate regenerative activities of endogenous cells and actively contribute to the wound healing processes.

The Clinical Profile of Patients with Psoriasis in Korea: A Nationwide Cross-Sectional Study (EPI-PSODE).

BACKGROUND: Psoriasis is an immune-mediated, chronic inflammatory disease affecting multiple aspects of patients' lives. Its epidemiology varies regionally; however, nationwide epidemiologic data on psoriasis depicting profile of Korean patients has not been available to date. OBJECTIVE: To understand nationwide epidemiologic characteristics and clinical features of adult patients with psoriasis visited university hospitals in Korea. METHODS: This multicenter, non-interventional, cross-sectional study recruited 1,278 adult patients with psoriasis across 25 centers in Korea in 2013. Various clinical data including PASI, BSA, DLQI, SF-36 and PASE were collected. RESULTS: A total of 1,260 patients completed the study (male:female=1.47:1). The mean age was 47.0 years with a distribution mostly in the 50s (24.9%). Early onset (<40 years) of psoriasis accounted for 53.9% of patients. The mean disease duration was 109.2 months; mean body mass index was 23.9 kg/m2; and 12.7% of patients had a family history of psoriasis. Plaque and guttate types of psoriasis accounted for 85.8% and 8.4%, respectively. Patients with PASI ≥10 accounted for 24.9%; patients with body surface area ≥10 were 45.9%. Patients with DLQI ≥6 accounted for 78.8%. Between PASI <10 and PASI ≥10 groups, significant difference was noted in age at diagnosis, disease duration, blood pressure, waist circumference of female, and treatment experiences with phototherapy, systemic agents, and biologics. CONCLUSION: This was the first nationwide epidemiologic study of patients with psoriasis in Korea and provides an overview of the epidemiologic characteristics and clinical profiles of this patient population.

Mental-Physical Comorbidity in Korean Adults: Results from a Nationwide General Population Survey in Korea.

OBJECTIVE: The aims of this study were to estimate the prevalence of mental-physical comorbidity and health-threatening risk factors in subjects with mental disorders, and the risks of mental disorders in those with physical diseases for the last 12 months in the general Korean population. METHODS: Korean Epidemiologic Catchment Area study replication (KECA-R) was conducted for 6,510 adults between August 2006 and April 2007. The Korean version of Composite International Diagnostic Interview 2.1 (K-CIDI) was used in the survey. Prevalence of mental and physical disorders, and risk factors for physical health were calculated, and their associations were evaluated with adjustment for age and sex. RESULTS: Subjects with any mental disorder showed significantly higher prevalence of chronic physical conditions (adjusted odds ratio, AOR=1.5 to 2.8, p<0.001) and medical risk factors including smoking, heavy drinking, overweight, and hypertension (AOR=1.5 to 4.0, p<0.001). Of those with chronic physical conditions, 21.6% had one or more comorbid mental disorder compared with 10.5% of the subjects without chronic physical disorders (AOR=2.6, p<0.001). Contrary to expectations, depressive disorders did not show significant association with hypertension and prevalence of obesity was not influenced by presence of mental disorders. Further studies should assess these findings. CONCLUSION: This is the first identification of significant mental-physical comorbidity in the general Korean population. Clinicians and health care officials should keep in mind of its potential adverse effects on treatment outcome and aggravated disease-related socioeconomic burden.

Fractional Laser-Assisted Topical Imiquimod 5% Cream Treatment for Recalcitrant Common Warts in Children: A Pilot Study.

BACKGROUND: Conventional treatments for warts like cryotherapy are limited by the pain during procedures, especially in pediatric patients. Imiquimod is a topical immune response modifier, but the thick stratum corneum of common warts prevents drug permeation through skin. OBJECTIVE: To evaluate the efficacy and safety of fractional laser/topical 5% imiquimod cream for the treatment of warts in children. METHODS: Eleven pediatric patients with multiple recalcitrant common warts were included. Lesions were treated using an ablative fractional 2,940-nm Er:YAG laser at 1- or 2-week interval. After each laser treatment session, imiquimod 5% cream was self-applied once daily 5 days a week. Response and adverse effects were assessed 2 weekly until complete clearance or up to maximum of 48 weeks. Pain during fractional laser was assessed using a visual analogue scale (0-10). RESULTS: Eight of the 11 (72.7%) children experienced complete clearance. Mean duration was 29.7 (16-48) weeks, and the mean number of fractional laser was 17.5 (8-37). No significant adverse effect was observed. Pain visual analogue scale during fractional laser was 2.4 (1-4) compared to 6.2 (5-8) during cryotherapy. CONCLUSION: This pilot study indicates that fractional laser-assisted topical imiquimod may provide benefit for recalcitrant warts in children.

Adverse events associated with acupuncture: a clinicopathologic review.

BACKGROUND: Acupuncture is one of the most popular modalities used to treat various diseases in traditional Korean and Oriental medicine. However, its risk of adverse events can be easily overlooked. OBJECTIVE: We investigated dermatological adverse events associated with acupuncture to draw attention to the risk of such adverse events. METHODS: We evaluated the types of acupuncture, clinicopathologic diagnoses, treatments, and prognoses in patients with a causal relationship between acupuncture and dermatoses. RESULTS: The study population comprised 25 patients (mean age, 52 years) with a history of acupuncture. Bee venom acupuncture was performed the most frequently (13 of 25 patients), and most patients received acupuncture to control pain (19 of 25 patients). The most common adverse event was infectious skin disease such as atypical mycobacterial infection or pyoderma/abscess, followed by hypersensitivity reactions, localized lipoatrophy, and hypertrophic scar. Acupuncture-related dermatoses required a relatively long treatment period (average, 8.6 weeks). CONCLUSION: Various dermatoses may occur following acupuncture. To minimize the risk of these dermatoses, proper training and medical knowledge in acupuncture practice are necessary for medical personnel. Dermatologists, oriental medical practitioners, and patients should pay attention to the potential adverse events of acupuncture.

Mesenchymal Stem Cells Aggregate and Deliver Gold Nanoparticles to Tumors for Photothermal Therapy.

Gold nanoparticles (AuNPs) have been extensively studied for photothermal cancer therapy because AuNPs can generate heat upon near-infrared irradiation. However, improving their tumor-targeting efficiency and optimizing the nanoparticle size for maximizing the photothermal effect remain challenging. We demonstrate that mesenchymal stem cells (MSCs) can aggregate pH-sensitive gold nanoparticles (PSAuNPs) in mildly acidic endosomes, target tumors, and be used for photothermal therapy. These aggregated structures had a higher cellular retention in comparison to pH-insensitive, control AuNPs (cAuNPs), which is important for the cell-based delivery process. PSAuNP-laden MSCs (MSC-PSAuNPs) injected intravenously to tumor-bearing mice show a 37-fold higher tumor-targeting efficiency (5.6% of the injected dose) and 8.3 °C higher heat generation compared to injections of cAuNPs after irradiation, which results in a significantly enhanced anticancer effect.

Decursin from Angelica gigas Nakai Inhibits B16F10 Melanoma Growth Through Induction of Apoptosis.

Decursin, a bioactive phytochemical isolated from Angelica gigas Nakai (danggwi), has shown preclinical anticancer efficacy in various cancer models. However, the antitumor effect of decursin in melanoma models remains undefined. The antitumor activities of decursin were investigated in B16F10 cells in vitro and in vivo. In this study, we show that treatment with decursin inhibited cell proliferation in a dose-dependent manner in B16F10 cells, but not in normal cells. Decursin also induced apoptosis in B16F10 cells, as determined by annexin V-staining assay and transferase-mediated nick-end labeling (TUNEL) staining assay. Decursin increased the phosphorylation of p38 as well as the expression of Bax while decreasing the phosphorylation of extracellular signaling-regulated kinase (ERK) and the expression of Bcl-2 in B16F10 cells. Moreover, decursin activated caspase-3 in B16F10 cells and xenograft tumor tissue. Together, these findings support further investigations into the potential use of decursin in the treatment of melanoma cells.

Erythrodermic Psoriasis Treated with Golimumab: A Case Report.

Erythrodermic psoriasis (EP) is a very severe variant of psoriasis whose management poses a challenge to physicians, as currently available therapies often provide unsatisfactory results. Many biologics have been used to treat chronic plaque psoriasis, the most common form of psoriasis; however, their effectiveness for EP is poorly understood. A recently developed biologic, golimumab, has been extensively studied for the treatment of moderate-to-severe active rheumatoid arthritis, psoriatic arthritis, active ankylosing spondylitis, and chronic plaque psoriasis. However, no clinical trials have been performed for EP. Here, we report the case of a 32-year-old man who presented with severe psoriasis that previously failed to respond satisfactorily to methotrexate, cyclosporine, retinoid, narrow-band ultraviolet B phototherapy, and topical agents (i.e., steroids and calcipotriol). Skin lesions worsened progressively and developed into erythroderma. Psoriatic arthritis was also detected. Conventional therapies lacked efficacy. Therefore, we administered golimumab 50 mg. The skin lesions improved significantly according to the Psoriasis Area and Severity Index score after the first administration; lesions improved further throughout the treatment course. Although additional studies are required to fully evaluate the efficacy and safety of golimumab, this agent may be an alternative treatment strategy for some patients with recalcitrant EP.

Extensive psoriasis induced by pegylated interferon alfa-2a and ribavirin in the treatment of chronic hepatitis C.

A 56-year-old man with chronic hepatitis C was treated with pegylated interferon alfa-2a in combination with ribavirin. However, psoriatic lesions appeared and worsened dramatically during therapy. Because of the extensive skin eruptions, he stopped therapy for chronic hepatitis C and subsequently started narrow-band ultraviolet B phototherapy and topical calcipotriol/betamethasone dipropionate ointment. After this, the psoriasis improved in a slow but comprehensive manner. Our case suggests that physicians should keep in mind the possibility of psoriasis as a side effect of interferon treatment for chronic hepatitis C.

Is narrowband ultraviolet B monotherapy effective in the treatment of pityriasis lichenoides?

BACKGROUND: Pityriasis lichenoides (PL) is a self-limiting papulosquamous disease that may persist for years and is associated with a high relapse rate. To date, few comparative studies have investigated the efficacy of narrowband ultraviolet B (NB-UVB) phototherapy and other therapies in the treatment of PL. OBJECTIVES: The present study retrospectively compared the clinical efficacies of NB-UVB phototherapy, systemic therapy, and a combination of NB-UVB and systemic medication in the treatment of PL. METHODS: Seventy patients diagnosed with PL were enrolled in this study. They were divided into three subgroups: the NB-UVB treatment group; the systemic treatment group; and the combination treatment group. Therapeutic efficacy was evaluated according to whether the subjects demonstrated a complete response (> 90% improvement in skin lesions), partial response (50-90% improvement), or no response (< 50% improvement) to treatment. RESULTS: A 91.9% complete response rate was achieved in the NB-UVB group, whereas only 69.2 and 80.0% of patients achieved a complete response in the systemic and combination treatment groups, respectively; these differences were not statistically significant. The mean treatment periods were 8.3, 5.3, and 7.9 weeks in the NB-UVB, systemic, and combination treatment groups, respectively; these differences were also not significant. CONCLUSIONS: Monotherapy using NB-UVB is effective in achieving a complete response in the treatment of PL and thus eliminates the need for concurrent systemic medication.

pH-responsive assembly of gold nanoparticles and "spatiotemporally concerted" drug release for synergistic cancer therapy.

A challenge in using plasmonic nanostructure-drug conjugates for thermo-chemo combination cancer therapy lies in the huge size discrepancy; the size difference can critically differentiate their biodistributions and hamper the synergistic effect. Properly tuning the plasmonic wavelength for photothermal therapy typically results in the nanostructure size reaching ∼100 nm. We report a new combination cancer therapy platform that consists of relatively small 10 nm pH-responsive spherical gold nanoparticles and conjugated doxorubicins. They are designed to form aggregates in mild acidic environment such as in a tumor. The aggregates serve as a photothermal agent that can selectively exploit external light by their collective plasmon modes. Simultaneously, the conjugated doxorubicins are released. The spatiotemporal concertion is confirmed at the subcellular, cellular, and organ levels. Both agents colocalize in the cell nuclei. The conjugates accumulate in cancer cells by the rapid phagocytic actions and effective blockage of exocytosis by the increased aggregate size. They also effectively accumulate in tumors up to 17 times over the control because of the enhanced permeation and retention. The conjugates exhibit a synergistic effect enhanced by nearly an order of magnitude in cellular level. The synergistic effect is demonstrated by the remarkable reductions in both the therapeutically effective drug dosage and the photothermal laser threshold. Using an animal model, effective tumor growth suppression is demonstrated. The conjugates induce apoptosis to tumors without any noticeable damage to other organs. The synergistic effect in vivo is confirmed by qRT-PCR analysis over the thermal stress and drug-induced growth arrest.

Korean red ginseng powder in the treatment of melasma: an uncontrolled observational study.

Exposure to the sun, ultraviolet radiation, and oxidative stress are the chief etiologic factors responsible for melasma. The ingredients of Korean red ginseng powder, which include ginsenoside and phenolic compounds, have antioxidative effects and reduce ultraviolet B-induced pigmentation. This study was designed to evaluate the effectiveness and safety of Korean red ginseng powder in patients with melasma. In 25 female patients, 3 g of Korean red ginseng powder was orally administered for a 24 week period. The level of pigmentation and erythema were determined and clinical improvement was evaluated by the melasma area and severity index (MASI), melasma quality of life scale (MELASQoL), and patient- and investigator-rated global improvement scale. After 24 weeks, the MASI score decreased from 8.8 to 5.6, and MELASQoL showed improvement in 91% of patients (p<0.05). The mean level of pigmentation decreased from 184.3 to 159.7 and erythema levels decreased from 253.6 to 216.4 (p<0.05). Additionally, 74% of the patients showed some improvement in both patient- and investigator-rated global improvement scales at week 24. Korean red ginseng powder was well tolerated by most of the patients. In conclusion, Korean red ginseng powder showed good tolerability and beneficial effects in patients with melasma. The use of Korean red ginseng would be counted as a useful adjunctive therapy for patients with melasma.

Cyclic mechanical strain promotes transforming-growth-factor-beta1-mediated cardiomyogenic marker expression in bone-marrow-derived mesenchymal stem cells in vitro.

Cardiomyocytes in the heart reside in mechanically dynamic environments, such as those subject to cyclic mechanical strain. TGF-beta1 (transforming growth factor-beta1) stimulates cardiomyogenic marker expression of BMMSCs (bone-marrow-derived mesenchymal stem cells). In the present study, we tested the hypothesis that cyclic mechanical strain promotes TGF-beta1-mediated cardiomyogenic marker expression in BMMSCs in vitro. The mRNA expression of cardiac-specific genes was more up-regulated in BMMSCs cultured with a TGF-beta1 supplement and subjected to cyclic strain for 1 week than in BMMSCs cultured statically with a TGF-beta1 supplement. Immunocytochemical analyses and flow cytometric analysis showed that the proportions of cardiac troponin-I-positive cells and cardiac MHC (myosin heavy chain)-positive cells and the proportions of cells expressing tropomyosin respectively were increased to a greater extent by TGF-beta1with cyclic strain than by TGF-beta1 alone. These results showed that cyclic strain promotes TGF-beta1mediated cardiomyogenic marker expression in BMMSCs in vitro.

Changing patterns of prognosticators during 15-year follow-up of advanced gastric cancer after radical gastrectomy and adjuvant chemotherapy: a 15-year follow-up study at a single korean institute.

BACKGROUND: We evaluated the long-term natural history of gastric cancer after radical gastrectomy and adjuvant chemotherapy through a 15-year follow-up study at a single institute. METHODS: Five hundred patients with advanced gastric adenocarcinoma who received radical gastrectomy and adjuvant chemotherapy were included in this long-term follow-up study. Patients were evaluated by imaging studies and upper gastrointestinal series or endoscopy every 6 months until the 10th year after surgery. Since then, the patients have been followed yearly in the same manner. RESULTS: The median follow-up period was 190.5 months. The recurrence rate in 5-year survivors was 10.8%. The dominant recurrence pattern was peritoneal carcinomatosis within 5 years and distant metastasis after 5 years post gastrectomy. Tumor stage was a clear-cut prognosticator within 5 years post gastrectomy, but was no longer informative in 5-10 years. At this period, only stage IV (IB-IIIB vs IVM0) was a significantly poor prognosticator. After 10 years, second primary cancer (seven cases) became as important an issue as recurrence of primary gastric cancer (six cases). CONCLUSIONS: In patients with gastric carcinoma treated with radical gastrectomy and adjuvant chemotherapy, late recurrence after 5 years post gastrectomy was not rare. Prognosticators were varied depending on the length of time after surgery. Tumor factors including stage were prognosticators within 5 years post gastrectomy, but tumor factors except stage IV had no prognostic value after 5 years. In the 5-10 years post gastrectomy, only stage IV (IB-IIIB vs IVM0) was a poor prognosticator. Also, after 10 years, there were no prognosticators.